Normal bone remodeling involves the precise and simultaneous control of bone formation and bone resorption cycles. Although systemic humoural factors are important in modulating the cellular activities affecting these cycles, local regulatory mechanisms determine their dynamics at a given site. These local regulatory mechanisms are controlled by complex cell/matrix and cell/cell interactions involving the behavior of osteoblasts, osteocytes, osteoclasts, macrophages and lymphocytes. Compelling evidence now exists to suggest a significant role for mast cells in this process. Experiments have been designed to test the hypothesis that periosteal mast cells are involved in the local control of bone remodeling cycles and, further, that selective contacts between mast cells and other cell types in the periosteum are critical in determining the mast cell's affect on this process. The experiments will focus on the following goals: (1) Light and electron microscopic techniques will be used to determine the distribution of periosteal mast cels in relationship to the adjacent underlying bone matrix, and in relationship to the other cellular constituents of normal periosteum during postnatal development of mouse calvarium. (2) Histomorphometric methods (both light and electron microscopic) will be utilized to quantify the profile of selective cell/cell contacts between mast cells and other cell types during each phase of the remodeling cycle in alveolar bone during experimentally-induced tooth egression. (3) Organ cultures of neonatal mouse calvaria will be employed to study the influence of mast cells on bone remodelling; mast cell-deficient mutants (W/Wv) will be compared to their normal littermates with respect to the action of hormones and/or compound 48/80 on bone resorption and formation, as assessed by the release of previously incorporated 45calcium, and the incorporation of (14C)-proline into collagenase digestible protein, respectively. These studies are intended to further elucidate the cellular interactions that control the local sequence of events during bone remodeling cycles; determining the role of mast cells may lead to a better understanding of the cellular dysfunctions contributing to bone diseases such as chronic destructive periodontitis and osteoporosis.